Simvastatin (Page 3 of 10)


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D. R. Taves, Minimization: A New Method of Assigning Patients To Treatment and Control Groups. Clin. Pharmacol. Ther. 15 (1974), pp. 443-453

Angiographic Studies

In the Multicenter Anti-Atheroma Study, the effect of simvastatin on atherosclerosis was assessed by quantitative coronary angiography in hypercholesterolemic patients with coronary heart disease. In this randomized, double-blind, controlled study, patients were treated with simvastatin 20 mg/day or placebo. Angiograms were evaluated at baseline, two and four years. The co-primary study endpoints were mean change per-patient in minimum and mean lumen diameters, indicating focal and diffuse disease, respectively. Simvastatin significantly slowed the progression of lesions as measured in the Year 4 angiogram by both parameters, as well as by change in percent diameter stenosis. In addition, simvastatin significantly decreased the proportion of patients with new lesions and with new total occlusions.

Modifications of Lipid Profiles

Primary Hypercholesterolemia (Fredrickson type IIa and IIb)

Simvastatin has been shown to be highly effective in reducing total-C and LDL-C in heterozygous familial and non-familial forms of hypercholesterolemia and in mixed hyperlipidemia. A marked response was seen within 2 weeks, and the maximum therapeutic response occurred within 4-6 weeks. The response was maintained during chronic therapy. Simvastatin consistently and significantly decreased total-C, LDL-C, total-C/HDL-C ratio, and LDL-C/HDL-C ratio; simvastatin also decreased TG and increased HDL-C (see Table 2).

TABLE 2
Mean Response in Patients with Primary Hypercholesterolemia and Combined (mixed) Hyperlipidemia(Mean Percent Change from Baseline After 6 to 24 Weeks)
TREATMENT N TOTAL-C LDL-C HDL-C TG *
*
median percent change
mean baseline LDL-C 244 mg/dL and median baseline TG 168 mg/dL
mean baseline LDL-C 188 mg/dL and median baseline TG 128 mg/dL
§
mean baseline LDL-C 226 mg/dL and median baseline TG 156 mg/dL
mean baseline LDL-C 156 mg/dL and median baseline TG 391 mg/dL.
Lower Dose Comparative Study (Mean % Change at Week 6)
Simvastatin 5 mg q.p.m 109 -19 -26 10 -12
Simvastatin 10 mg q.p.m. 110 -23 -30 12 -15
Scandinavian Simvastatin Survival Study (Mean % Change at Week 6)Placebo 2223 -1 -1 0 -2
Simvastatin 20 mg q.p.m. 2221 -28 -38 8 -19
Upper Dose Comparative Study § (Mean % Change Averaged at Weeks 18 and 24)
Simvastatin 40 mg q.p.m. 433 -31 -41 9 -18
Simvastatin 80 mg q.p.m. 664 -36 -47 8 -24
Multi-Center Combined Hyperlipidemia Study (Mean % Change at Week 6)
Placebo 125 1 2 3 -4
Simvastatin 40 mg q.p.m. 123 -25 -29 13 -28
Simvastatin 80 mg q.p.m. 124 -31 -36 16 -33

In the Upper Dose Comparative Study, the mean reduction in LDL-C was 47% at the 80-mg dose. Of the 664 patients randomized to 80 mg, 475 patients with plasma TG ≤ 200 mg/dL had a median reduction in TG of 21%, while in 189 patients with TG > 200 mg/dL, the median reduction in TG was 36%. In these studies, patients with TG > 350 mg/dL were excluded.

Hypertriglyceridemia (Fredrickson type IV)

The results of a subgroup analysis in 74 patients with type IV hyperlipidemia from a 130-patient, double-blind, placebo-controlled, 3-period crossover study are presented in Table 3.

TABLE 3
Six-week, Lipid-lowering Effects of Simvastatin in Type IV HyperlipidemiaMedian Percent Change (25th and 75th percentile) from Baseline *
TREATMENT N Total-C LDL-C HDL-C TG VLDL-C Non-HDL-C
*
The median baseline values (mg/dL) for the patients in this study were: total-C = 254, LDL-C = 135, HDL-C = 36, TG = 404, VLDL-C = 83, and non-HDL-C = 215.
Placebo 74 +2 +1 +3 -9 -7 +1
(-7, +7) (-8, +14) (-3, +10) (-25, +13) (-25, +11) (-9, +8)
Simvastatin 40 mg/day 74 -25 -28 +11 -29 -37 -32
(-34, -19) (-40, -17) (+5, +23) (-43, -16) (-54, -23) (-42, -23)
Simvastatin 80 mg/day 74 -32 -37 +15 -34 -41 -38
(-38, -24) (-46, -26) (+5, +23) (-45, -18) (-57, -28) (-49, -32)

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